Consent rules can have fatal consequences, say UK researchers

The current rules for obtaining informed consent in clinical trials may result in life-threatening delays to treatment in emergency situations, UK researchers have warned.

The warning comes in a letter to The Lancet from Professor Ian Roberts, Dr Haleema Shakur and Dr David Prieto-Merino of the Clinical Trials Unit at the London School of Hygiene & Tropical Medicine, as well as Sir Iain Chalmers of the James Lind Initiative and Professor Jon Nicholl from the University of Sheffield.

In cases of severe trauma, argue Roberts et al, waiting for a relative to grant written permission for a patient to take part in a trial is “unethical” in view of the importance of prompt treatment.

The researchers analysed data from CRASH-2, a large international placebo-controlled trial that evaluated the effects of a short course of tranexamic acid on death, vascular occlusive events and blood transfusions in trauma patients with significant haemorrhage.

Roberts was the clinical co-ordinator and chief investigator while Shakur was the trial manager for CRASH-2, results of which were published in The Lancet in June 2010.

Roberts et al found that initiation of treatment was delayed by more than an hour where written consent from relatives was required. Around one sixth of patients in the CRASH-2 trial missed out on the chance to benefit from a life-saving treatment due to what the authors termed “consent rituals”.

The need for urgent treatment, even in patients who are conscious and whose relatives are available, “excludes the possibility of fully informed consent”, the letter states. “If consent rituals delay the start of a trial treatment such that the treatment effect could be reduced or obscured, we maintain that seeking consent is actually unethical.”

These potentially “lethal effects” might have been highlighted decades ago “had the research ethics community accepted a responsibility to provide robust evidence that its prescriptions are likely to do more good than harm”, Roberts and his colleagues write.

EU Directive review

The issue of applying more flexible rules for informed consent in emergency clinical trials has been addressed in the European Commission’s review of the much-maligned EU Clinical Trials Directive, 2001/20/EC.

In a concept paper on planned revisions to the Directive issued earlier this year, the Commission noted that conditions for emergency clinical trials were “extensively explored” in the full public consultation on the clinical trials legislation launched in October 2009.

The Directive needs to take into account internationally agreed documents such as the World Medical Association’s Declaration of Helsinki, the Council of Europe’s Convention on Human rights and Biomedicine, and the International Conference on Harmonisation’s Guidelines on Good Clinical Practice, all of which “explicitly

Accordingly, the Directive could be amended, the Commission suggested, so that informed consent and the provision of information by the investigator occur either during or after the clinical trial when:

- The trial subject is not in a state to give informed consent.

- Physical or mental conditions that stand in the way of informed consent are

a necessary characteristic of the research population.

- Due to the urgency of the situation, it is impossible to obtain informed

consent from the patient’s parents or legal representative in accordance with the Clinical Trials Directive, and is impossible to convey the

informationp rovided for in the Directive.

- The trial subject has not previously expressed any objections known to the

investigator.

In these cases, the concept paper proposed, informed consent would have to be obtained as soon as possible from the parents/legal representative or from the trial subject (whichever is the quickest).